Table 2.
Studies assessing effects of blood Phe on executive function in adults with PKU.
| First Author, Year, [Reference] | N | Population and Treatment | Blood Phe (µmol/L) Mean ± SD (range) |
Results in Low Blood Phe vs. High Blood Phe Cohorts |
|---|---|---|---|---|
| Intervention Studies (Single Cohort) | ||||
| Lou et al. (1987) | 9 | Early- (5) and late-treated (4), off diet | 1477 (980–2050) |
6 of 7 participants with abnormally long continuous visual reaction times on regular diet showed improved reaction times on low-Phe diet (means: 34.6 vs. 31.6 1/100 sec) |
| After 3 weeks on low-Phe diet | 758 (456–1052) |
|||
| Pietz et al. (1993) | 5 | Early-treated, off diet | 1600 (1290–2130) |
On low-Phe diet, participants showed improved scores for attention (Dot Pattern Exercise: 8.8 vs. 11.7) and cognitive flexibility (Color Pattern Exercise) |
| After 4 weeks on low-Phe diet | 753 (515–1023) |
|||
| Schmidt et al. (1994) | 14 | Early-treated, off diet | 1332 (569–1949) |
On low-Phe diet, participants showed significantly improved scores for attention (Dot Pattern Exercise: 8.1 vs. 10.1, p < 0.001) |
| After 4 weeks on low-Phe diet | 636 (121–1017) |
|||
| ten Hoedt et al. (2011) | 9 | Early and continuous treatment | on diet: 709 ± 332 |
Phe loading resulted in a significant larger fluctuation in tempo during sustained attention (p = 0.029), but had no significant effect on other measures (Amsterdam Neuropsychological Tasks) |
| 4-Week Phe load | Phe load: 1259 ± 332 |
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| Studies Comparing Cohorts with Low and High Blood Phe | ||||
| Bik-Multanowski et al. (2011) | 22 | Early-treated | ≤720 | Low Phe cohort showed improved scores for working memory (Spatial Span: −1.09 SD vs. −2.92 SD), attention (Rapid Visual Info: −1.59 SD vs. −2.49 SD), and inhibitory control (Stop Signal accuracy: 0.68 vs. 0.60) |
| 27 | Early-treated | >720 | ||
| Brumm et al. (2004) | 11 | Early-treated | <1000 | When comparing low vs. high Phe cohorts the following reached or neared statistical significance: Attention (CPT Omission Errors 49.7 vs 65.5 and CPT response rate 57.8 vs. 37.3), language function (BNT 40.8 vs 13.1, COWAT 22.7 vs. 5.3, Animal Naming Test 21.9 vs. 16.9, PPVT-R 67.5 vs. 39.9, WAIS-R Vocabulary 67.3 vs. 47.7), psychomotor speed (WAIS-R Digit Symbol 68.8 vs. 48.7). |
| 13 | Early-treated | >1000 | ||
| Burgard et al. (1997) | 8 | Early, continuously treated | 870 (569–1150) |
Low Phe cohort showed significantly improved scores for attention (Dot Pattern Exercise: 8.7 vs. 10.2) |
| 8 | Early-treated, off diet | 1350 (1029–1876) |
||
| Channon et al. (2007) | 25 | Early, continuously treated | 759 (221–1233) |
Low Phe cohort showed significantly improved scores for working memory (2-back [% accuracy]: 88.9 vs. 84.6, p < 0.01) and attention (0-back [% accuracy]: 98.8 vs. 97.1, p < 0.01), but not cognitive flexibility (Object Alteration [% correct trials]: 66.5 vs. 60.2). Low Phe cohort results were mixed for inhibitory control, with significantly better results for speed (Flanker [speed]: 0.45 vs. 49, .47 vs. .52; p < 0.01) but deficits in accuracy (Flanker [% accuracy]: 99.4 vs. 98.0) |
| 25 | early-treated, off diet | 1286 (990–1651) |
||
| Dawson et al. (2011) | 21 | Early, continuously treated | 640 ± 103 | Low Phe cohort showed improved scores for reaction time (saccadic latency: 6.0 vs. 5.6). Reaction times for low Phe cohort did not differ from unaffected controls (p = 0.82), while those for high Phe cohort were significantly worse (p = 0.02) |
| 56 | Early-treated, off diet | 1461 ± 185 | ||